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Open Access Research article

Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer's disease or vascular dementia: a case-control study

Giovanni Zuliani12*, Michela Perrone Donnorso3, Cristina Bosi1, Angelina Passaro1, Edoardo Dalla Nora1, Amedeo Zurlo4, Francesco Bonetti1, Alessia F Mozzi3 and Claudio Cortese3

Author Affiliations

1 Department of Clinical and Experimental Medicine, Section of Internal Medicine, Gerontology and Clinical Nutrition; Azienda Ospedaliero-Universitaria Arcispedale S. Anna, Ferrara, Italy

2 Associazione Alzheimer-Perusini, Ferrara, Italy

3 Department of Clinical Biochemistry and Molecular Biology, University of Rome 2, Tor Vergata, Italy

4 Geriatrics Division; Azienda Ospedaliero-Universitaria Arcispedale S. Anna, Ferrara, Italy

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BMC Neurology 2011, 11:121  doi:10.1186/1471-2377-11-121

Published: 4 October 2011

Abstract

Background

In central nervous system cholesterol cannot be degraded but is secreted into circulation predominantly in the form of its polar metabolite 24(S)-hydroxycholesterol (24S-OH-Chol). Some studies suggested an association between 24S-OH-Chol metabolism and different neurological diseases including dementia. A possible decrease in 24S-OH-Chol plasma levels has been reported late onset Alzheimer's disease (LOAD) and vascular dementia (VD), but results of previous studies are partially contradictory.

Methods

By high-speed liquid chromatography/tandem mass spectrometry we evaluated the plasma levels of 24S-OH-Chol in a sample of 160 older individuals: 60 patients with LOAD, 35 patients with VD, 25 subjects affected by cognitive impairment no-dementia (CIND), and 40 (144 for genetics study) cognitively normal Controls. We also investigated the possible association between PPARgamma Pro12Ala polymorphism and dementia or 24S-OH-Chol levels.

Results

Compared with Controls, plasma 24S-OH-Chol levels were higher in LOAD and lower in VD; a slight not-significant increase in CIND was observed (ANOVA p: 0.001). A positive correlation between 24S-OH-Chol/TC ratio and plasma C reactive protein (CRP) levels was found in the whole sample, independent of possible confounders (multiple regression p: 0.04; r2: 0.10). This correlation was strong in LOAD (r: 0.39), still present in CIND (r: 0.20), but was absent in VD patients (r: 0.08). The PPARgamma Pro12Ala polymorphism was not associated with the diagnosis of LOAD, VD, or CIND; no correlation emerged between the Ala allele and 24S-OH-Chol plasma levels.

Conclusions

Our results suggest that plasma 24S-OH-Chol levels might be increased in the first stages of LOAD, and this phenomenon might be related with systemic inflammation. The finding of lower 24S-OH-Chol concentrations in VD might be related with a more advanced stage of VD compared with LOAD in our sample, and/or to different pathogenetic mechanisms and evolution of these two forms of dementia.